Mohammed Shurrab1,2,3,4, Cynthia A Jackevicius5,6,7,8, Peter C Austin5,6, Karen Tu5,9,10,11, Feng Qiu6, Joseph Caswell12,6, Faith Michael13, Jason G Andrade14,15, Dennis T Ko5,6,16. 1. Cardiology Department, Health Sciences North, Northern Ontario School of Medicine, Sudbury, ON, Canada. shurrabm@hotmail.com. 2. Health Sciences North Research Institute, Sudbury, ON, Canada. shurrabm@hotmail.com. 3. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. shurrabm@hotmail.com. 4. ICES, Toronto, ON, Canada. shurrabm@hotmail.com. 5. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. 6. ICES, Toronto, ON, Canada. 7. Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA. 8. Pharmacy Department, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. 9. North York General Hospital, Toronto, ON, Canada. 10. Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada. 11. University Health Network-Toronto Western Hospital Family Health Team, Toronto, ON, Canada. 12. Health Sciences North Research Institute, Sudbury, ON, Canada. 13. Cardiology Department, Health Sciences North, Northern Ontario School of Medicine, Sudbury, ON, Canada. 14. Heart Rhythm Services, Department of Medicine, University of British Columbia, Vancouver, Canada. 15. Center for Cardiovascular Innovation, Vancouver, Canada. 16. Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Abstract
BACKGROUND: Diltiazem is a commonly used medication in patients with atrial fibrillation (AF) with potential for a drug-drug interaction (DDI) with direct oral anticoagulants (DOACs). We aimed to assess the risk of major bleeding after co-prescription of diltiazem and DOACs among adults with AF. METHODS: We conducted a population-based, nested case-control study in Ontario, Canada. The study population included all patients with AF > 66 years on a DOAC between April 1, 2011, and March 31, 2018. Cases were patients admitted with major bleeding (index date). Each case was matched to two controls. We categorized exposure to diltiazem before the index date as: (a) current users (diltiazem use within 7 days); (b) recent users (diltiazem use within 8 to 90 days); and (c) unexposed (no diltiazem prescription or diltiazem prescription > 90 days before index date). Conditional logistic regression models were used to examine the association between bleeding and diltiazem co-prescription. RESULTS: Among 86,679 AF patients on a DOAC, the median age of AF patients was 80 years (interquartile range 75-85); 48.3% were women. We identified 2,766 cases (3.2%) who were hospitalized with major bleeding. After multivariable adjustment, there was a significant association between major bleeding and current use of diltiazem (adjusted odds ratio (aOR) 1.37; 95% confidence interval (CI) 1.08-1.73, p < 0.009) but no significant association between major bleeding and recent use of diltiazem (aOR 1.19, 95% CI 0.99-1.42, p = 0.06) as compared with the unexposed group. CONCLUSIONS: Current use of diltiazem was associated with major bleeding among AF patients receiving a DOAC.
BACKGROUND: Diltiazem is a commonly used medication in patients with atrial fibrillation (AF) with potential for a drug-drug interaction (DDI) with direct oral anticoagulants (DOACs). We aimed to assess the risk of major bleeding after co-prescription of diltiazem and DOACs among adults with AF. METHODS: We conducted a population-based, nested case-control study in Ontario, Canada. The study population included all patients with AF > 66 years on a DOAC between April 1, 2011, and March 31, 2018. Cases were patients admitted with major bleeding (index date). Each case was matched to two controls. We categorized exposure to diltiazem before the index date as: (a) current users (diltiazem use within 7 days); (b) recent users (diltiazem use within 8 to 90 days); and (c) unexposed (no diltiazem prescription or diltiazem prescription > 90 days before index date). Conditional logistic regression models were used to examine the association between bleeding and diltiazem co-prescription. RESULTS: Among 86,679 AF patients on a DOAC, the median age of AF patients was 80 years (interquartile range 75-85); 48.3% were women. We identified 2,766 cases (3.2%) who were hospitalized with major bleeding. After multivariable adjustment, there was a significant association between major bleeding and current use of diltiazem (adjusted odds ratio (aOR) 1.37; 95% confidence interval (CI) 1.08-1.73, p < 0.009) but no significant association between major bleeding and recent use of diltiazem (aOR 1.19, 95% CI 0.99-1.42, p = 0.06) as compared with the unexposed group. CONCLUSIONS: Current use of diltiazem was associated with major bleeding among AF patients receiving a DOAC.
Authors: Kevin Hill; Ewa Sucha; Emily Rhodes; Marc Carrier; Amit X Garg; Ziv Harel; Gregory L Hundemer; Edward G Clark; Greg Knoll; Eric McArthur; Manish M Sood Journal: JAMA Intern Med Date: 2020-08-01 Impact factor: 21.873